Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease
Authors: Kimberly P. Newton, Laura A. Wilson, Nancy A. Crimmins, Mark H. Fishbein, Jean P. Molleston, Stavra A. Xanthakos, Cynthia Behling, Jeffrey B. Schwimmer, Donna Garner, Paula Hertel, Alicia Lawson, Yen Pham, Nicole Triggs, Kristin Bramlage, April Carr, Meghan McNeill, Marialena Mouzaki, Stavra Xanthakos, Adina Alazraki, Rebecca Cleeton, Maria Cordero, Saul Karpen, Miriam Vos, Laura Carr, Oscar W. Cummings, Kathryn Harlow, Ann Klipsch, Jean P. Molleston, Wendy Morlan, Emily Ragozzino, Cindy Sawyers, Angela Anthony, Mark H. Fishbein, Theresa Cattoor, Janet Freebersyser, Ajay K. Jain, Susan Torretta, Cynthia Behling, Janis Durelle, Nidhi P. Goyal, Kimberly P. Newton, Jeffrey B. Schwimmer, Patricia Ugalde-Nicalo, Andrew Wang, Niviann Blondet, Kara Cooper, Randolph Otto, Matthew Yeh, Melissa Young, David E. Kleiner, Edward C. Doo, Sherry Hall, Jay H. Hoofnagle, Averell H. Sherker, Rebecca Torrance, Patricia R. Robuck, Peggy Adamo, Patricia Belt, Jeanne M. Clark, Jill Meinert, Laura Miriel, Carrie Shade, Emily P. Sharkey, Jacqueline Smith, Michael Smith, Alice Sternberg, ScM; James Tonascia, Mark L. Van Natta, Annette Wagoner, Laura A. Wilson, Tinsay Woreta, Katherine P. Yates, John Dodge, Michele Donithan, Milana Isaacson
Journal: Clinical Gastroenterology and Hepatology (2022)

Background & AimsType 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.MethodsChildren with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.ResultsThis study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0–2.8]), associated with BMI z-score (HR, 1.8 [1.0–3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0–1.7]), and fibrosis stage (HR, 1.3 [1.0–1.5]).ConclusionsChildren with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed. Type 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors. Children with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection. This study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0–2.8]), associated with BMI z-score (HR, 1.8 [1.0–3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0–1.7]), and fibrosis stage (HR, 1.3 [1.0–1.5]). Children with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed.